In the human eye, a stable precorneal tear film is essential for maintenance of a healthy and comfortable ocular surface. Any breakdown in the precorneal tear film can result in symptoms of dryness, grittiness, irritation, burning, redness, itching, blurred vision, and photophobia in the eye, any of which may result in damage to both the cornea and conjunctiva.
The precorneal tear film is composed of three layers, the inner layer immediately adjacent to the ocular surface being a thin layer of mucin about 0.02 microns thick which is derived from goblet cells located in the conjunctiva. The intermediate layer is an aqueous layer about 7.0 microns thick which is derived from the lacrimal gland and from the accessory lacrimal gland and from the accessory lacrimal glands of Wolfring and Krause. The outermost layer is a layer of lipids about 0.1 microns thick which are derived from the meibomian glands lining the upper and lower eye lid margins. The meibomian glands continuously produce meibum material composed of numerous different types of lipids and the glands excrete the material onto the eyelid margin. The process of blinking spreads these lipids of the meibum material uniformly over the ocular surface to form the outer portion of the precorneal tear film.
Several different diseases can affect various portions of the precorneal tear film. For example, the Stevenss-Johnson syndrome can cause loss of goblet cells in the conjunctiva thereby resulting in the loss of the mucin layer. As a consequence, the tear film becomes extremely unstable and the resultant changes in the ocular surface may be severe. Similarly, keratoconjunctivitis sicca is loss of the aqueous component of the precorneal tear film, which results in profound drying changes on the ocular surface. Impairment of the secretion from meibomian glands also alters the stability of the precorneal tear film such that severe damage to the ocular surface through drying can result.
Meibum material primarily performs three functions in the eye. First, the material provides the lipids for the outermost layer of the precorneal tear film, which gives stability to the tear film. Second, meibum material retards evaporation of the aqueous phase of the precorneal tear film. Finally, meibum coats the lid margins, preventing the development of chronic irritation along the skin of the lids from constant wetting and drying from the aqueous tears. When the meibum content in the tear film is decreased, these functions may not be adequately performed by the remaining meibum. Specifically, break-up time of the precorneal tear film is increased, evaporation of the aqueous phase of the tear film is more rapid, and chronic irritation of the lid margins occurs.
The effects of decreased meibum can be best observed in those patients suffering from congenital ectodermal dysplasia, a rare abnormality which is associated with multiple developmental anomalies including partial or total absence of the meibomian glands. The resultant lack of meibum in the eyes of such patients causes an immediate break-up of the tear film, which results in severe changes of the ocular surface, including opacification of the cornea.
Another example of the lack of meibum is evident in patients suffering from chronic blepharitis, a fairly common condition, especially among the elderly. This condition is characterized by diffuse inflammation around the meibomian gland orifices due to lipid secretions solidifying within the glands, resulting in plugging of the orifices, with gland dilation and distortion. The lid margins becomes thickened and irregular, with dilated blood vessels. Tarsal injection with papillary hypertrophy, bulbar injection and superficial punctate keratopathy (SPK) frequently occur. The latter is attributed to an unstable tear film which is seen clinically by a rapid break-up time of the tear film. These changes in the tear film produce symptoms of burning, irritation, drying, grittiness and the like, as well as changes in visual acuity. The rapid break-up time may be neutralized by expressing fresh meibum from deep within the gland into the tear film.
As set forth above, the condition of meibomian gland dysfunction and its associated symptoms have been recognized for some time. Various treatments have been practiced over the years, present therapy primarily consisting of treatment of the lid margin disease through lid hygiene, and occasional use of antibiotic or steroid ointments, and oral tetracycline antibiotics. Symptoms of the disease are treated through various agents used for the supplementation of aqueous tears. In addition, ointments are often used that act primarily as sealants to the aqueous tear film. These ointments are usually composed of long-chain hydrocarbon products. However, long-chain hydrocarbons do not layer out in the precorneal tear film in a manner similar to meibum, and as a consequence, can cause severe blurring of vision. Thus, they can only be used when visual acuity is not of particular concern. Other treatments have included the frequent use of isotonic or hypotonic buffered saline, the application of viscoelastic materials, and the use of peanut oil.
It is, therefore, the primary object of the present invention to provide an improved ophthalmic composition and method for using same in the treatment in mammals of symptoms of meibomian gland dysfunction where insufficient meibum is produced, and thereby to restore the eye to a condition approximating that when sufficient meibum is produced.